A Service Integration Model of Value Creation: A Study of Commercial Online Communities

This paper presents a service integration model through a study of major for-profit online communities in both North America and China. Our study examines various types of communities and proposes particular means by which these communities might integrate their services with each other. Three integration strategies are identified: vertical integration, horizontal integration, and hybrid integration. The underlying mechanisms, as well as strategies that are needed to design and implement services, are also discussed

Mechanism underlying synergic activation of Tyrosinase promoter by MITF and IRF4

Background: The transcription factor interferon regulatory factor 4 (IRF4) was identified to be involved in human pigmentation by genome-wide association studies (GWASs). The rs12203592-[T/C], which is located in intron 4 of IRF4, shows the strongest link to these pigmentation phenotypes including freckling, sun sensitivity, eye and hair color. Previous studies indicated a functional cooperation of IRF4 with Microphthalmia-associated transcription factor (MITF), a causing gene of Waardenburg syndrome (WS), to synergistically trans-activate Tyrosinase (TYR). However, the underlying mechanism is still unknown. Methods: To investigate the importance of DNA binding in the synergic effect of IRF4. Reporter plasmids with mutant TYR promoters was generated to locate the IRF4 DNA binding sites in the Tyrosinase minimal promoter. By building MITF and IRF4 truncated mutations plasmids, the necessary regions of the synergy functions of these two proteins were also located. Results: The cooperative effect between MITF and IRF4 was specific for TYR promoter. The DNA-binding of IRF4 was critical for the synergic function. IRF4 DNA binding sites in TYR promoter were identified. The Trans-activation domains in IRF4 (aa134-207, aa300-420) were both important for the synergic function, whereas the auto-mask domain (aa207-300) appeared to mask the synergic effect. Mutational analysis in MITF indicated that both DNA-binding and transcriptional activation domains were both required for this synergic effect. Conclusions: Here we showed that IRF4 potently synergized with MITF to activate the TYR promoter, which was dependent on DNA binding of IRF4. The synergic domains in both IRF4 and MITF were identified by mutational analysis. This identification of IRF4 as a partner for MITF in regulation of TYR may provide an important molecular function for IRF4 in the genesis of melanocytes and the pathogenic mechanism in WS

Toward the chemoenzymatic synthesis of heparan sulfate oligosaccharides: oxidative cleavage of p-nitrophenyl group with ceric ammonium salts

We have developed an efficient chemoenzymatic synthesis of heparan sulfate oligosaccharides employing the para-nitrophenyl (p-NP) β-glucuronide as an acceptor compatible with enzymatic elongation and one that significantly simplifies oligosaccharide purification on C-18 resin. Employing ceric ammonium nitrate as oxidative reagent to remove the p-NP group unexpectedly also removed the glucuronic acid residue at the reducing-end, affording a smaller oligosaccharide. The application of ceric ammonium sulfate allowed the removal of the p-NP without concomitant loss of the adjacent glucuronic acid offering a route to longer heparin sulfate oligosaccharide products

Mesenchymal Stem Cell-Induced Immunoregulation Involves Fas Ligand/Fas-Mediated T Cell Apoptosis

Systemic infusion of bone marrow mesenchymal stem cells (BMMSCs) shows therapeutic benefit for a variety of autoimmune diseases, but the underlying mechanisms are poorly understood. Here we show that in mice systemic infusion of BMMSCs induced transient T-cell apoptosis via the Fas ligand (FasL)-dependent Fas pathway and could ameliorate disease phenotypes in fibrillin-1 mutated systemic sclerosis (SS) and dextran sulfate sodium-induced experimental colitis. FasL−/− BMMSCs did not induce T-cell apoptosis in recipients, and could not ameliorate SS and colitis. Mechanistic analysis revealed that Fas-regulated monocyte chemotactic protein 1 (MCP-1) secretion by BMMSCs recruited T-cells for FasL-mediated apoptosis. The apoptotic T-cells subsequently triggered macrophages to produce high levels of TGFβ which in turn led to the upregulation of Tregs and, ultimately, to immune tolerance. These data therefore demonstrate a previously unrecognized mechanism underlying BMMSC-based immunotherapy involving coupling via Fas/FasL to induce T-cell apoptosis

Pulsed laser-deposited n-Si/NiO_x photoanodes for stable and efficient photoelectrochemical water splitting

An electrocatalytic and stable nickel oxide (NiO_x) thin layer was successfully deposited on an n-Si (100) substrate by pulsed laser deposition (PLD), acting as a photoanode for efficient photo-oxidation of water under solar illumination. It was revealed that the formed n-Si/NiO_x heterojunction with good Schottky contact could improve photogenerated charge separation, and thus n-Si photoanodes deposited with a 105 nm-thick NiO_x electrocatalytic layer exhibited a photovoltage of ∼350 mV, leading to greatly improved photoelectrochemical performances for water oxidation. The stability of the photoanode was significantly enhanced with the increasing thickness of NiO_x protective layers. This study demonstrates a simple and effective method to enable the use of planar n-Si (100) substrates as efficient and durable photoanodes for practical solar water oxidation

Short-term effects of intravenous batroxobin in treatment of sudden sensorineural hearing loss: a propensity score-matched study

BackgroundSudden sensorineural hearing loss (SSNHL) can cause great panic in patients. Whether it is advantageous to add intravenous batroxobin in the treatment of SSNHL remains to be determined. This study aimed to compare the short-term efficacy of therapy combined with intravenous batroxobin and that without intravenous batroxobin in SSNHL patients.MethodsThis retrospective study harvested the data of SSNHL patients hospitalized in our department from January 2008 to April 2021. The hearing levels on the admitted day (before treatment) and the discharge day were considered pre-treatment hearing and post-treatment hearing, respectively. The hearing gain was the difference value of pre-treatment hearing and post-treatment hearing. We used Siegel's criteria and the Chinese Medical Association of Otolaryngology (CMAO) criteria to evaluate hearing recovery. The complete recovery rate, overall effective rate, and hearing gain at each frequency were considered outcomes. Propensity score matching (PSM) was conducted to balance the baseline characteristics between the batroxobin group and the non-batroxobin group. Sensitivity analysis was carried out in flat-type and total-deafness SSNHL patients.ResultsDuring the study period, 657 patients with SSNHL were admitted to our department. Among them, a total of 274 patients met the enrolled criteria of our study. After PSM, 162 patients (81 in each group) were included in the analysis. Once the hospitalized treatment was completed, the patients would be discharged the next day. Logistic regression analysis of the propensity score-matched cohort indicated that both the complete recovery rates [Siegel's criteria, OR: 0.734, 95% CI: 0.368–1.466, p = 0.381; CMAO criteria, OR: 0.879, 95% CI: 0.435–1.777, p = 0.720] and the overall effective rates [Siegel's criteria and CMAO criteria, OR: 0.741, 95% CI: 0.399–1.378, p = 0.344] were not significantly different between the two treatment groups. Sensitivity analysis has shown similar results. For flat-type and total-deafness SSNHL patients, no significant difference was found in post-treatment hearing gain at each frequency between the two groups after PSM.ConclusionThere was no significant difference in short-term hearing outcomes between treatment with batroxobin and treatment without batroxobin in SSNHL patients by Siegel's and CMAO criteria after PSM. Future studies for better therapy regimens of SSNHL are still needed

Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders, but impurities, structural heterogeneity or functional irreversibility can limit treatment options. We report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic methods. The high activity of one defined synthetic LMWH against human factor Xa (FXa) was reversible in vitro and in vivo using protamine, demonstrating that synthetically accessible constructs can have a critical role in the next generation of LMWHs

PwHAP5, a CCAAT-binding transcription factor, interacts with PwFKBP12 and plays a role in pollen tube growth orientation in Picea wilsonii

The HAP complex occurs in many eukaryotic organisms and is involved in multiple physiological processes. Here it was found that in Picea wilsonii, HAP5 (PwHAP5), a putative CCAAT-binding transcription factor gene, is involved in pollen tube development and control of tube orientation. Quantitative real-time reverse transcription-PCR showed that PwHAP5 transcripts were expressed strongly in germinating pollen and could be induced by Ca2+. Overexpression of PwHAP5 in pollen altered pollen tube orientation, whereas the tube with PwHAP5RNAi showed normal growth without diminishing pollen tube growth. Furthermore, PwFKBP12, which encodes an FK506-binding protein (FKBP) was screened and a bimolecular fluorescence complementation assay performed to confirm the interaction of PwHAP5 and PwFKBP12 in vivo. Transient expression of PwFKBP12 in pollen showed normal pollen tube growth, whereas the tube with PwFKBP12RNAi bent. The phenotype of overexpression of HAP5 on pollen tube was restored by FKBP12. Altogether, our study supported the role of HAP5 in pollen tube development and orientation regulation and identified FKBP12 as a novel partner to interact with HAP5 involved in the process